ALTERED EXPRESSION OF THE GROWTH AND TRANSFORMATION SUPPRESSOR PML GENE IN HUMAN HEPATOCELLULAR CARCINOMAS AND IN HEPATITIS TISSUES

The promyelocytic leukaemia (PML) gene, which encodes a transformation and growth suppressor, was first identified at a chromosomal transloc ation break point in acute promyelocytic leukaemia. To elucidate if PM L may be involved in hepatocellular carcinoma (HCC), the expression of PML was analysed using immunohistochemistry in human HCC and hepatiti s tissues. Our studies demonstrated overexpression of PML protein in t he PML-oncogenic domain (POD) structure in 50% of HCC (11/22). Enhance d expression and cytoplasmic localisation of PML was associated with c irrhosis. Increased expression of PML was also found in liver abscesse s. However, in colon metastasis to the liver, the expression of PML wa s moderate to low, although strong expression was seen in the surround ing interstitial cells, macrophages and lymphocytes, an indication of the inflammation process associated with tumour growth. Most interesti ngly, strong expression of PML was found in neoplastic cells at the pe riphery of the tumours, but progressively decreased in cells at the ce ntre of the tumours, which may be associated with an altered transform phenotype or apoptosis. The altered expression of PML indicates that this nuclear protein may play an important role in cellular response t o stress and inflammation, as well as in compensatory cell growth. (C) 1998 Elsevier Science Ltd. All rights reserved.